Fenfluramine‐induced serotonin release decreases [ 11 C]AZ10419369 binding to 5‐HT 1B ‐receptors in the primate brain

The need for positron emission tomography (PET)‐radioligands that are sensitive to changes in endogenous serotonin (5‐HT) levels in brain is recognized in experimental and clinical psychiatric research. We recently developed the novel PET radioligand [ 11 C]AZ10419369 that is highly selective for the 5‐HT 1B receptor. In this PET‐study in three cynomolgus monkeys, we examined the sensitivity of [ 11 C]AZ10419369 to altered endogenous 5‐HT levels. Fenfluramine‐induced 5‐HT release decreased radioligand binding in a dose‐dependent fashion with a regional average of 27% after 1 mg/kg and 50% after 5 mg/kg. This preliminary study supports that [ 11 C]AZ10419369 is sensitive to endogenous 5‐HT levels in vivo and may serve as a tool to examine the pathophysiology and treatment of major psychiatric disorders. Synapse 64:573–577, 2010. © 2010 Wiley‐Liss, Inc.